CN110256249B - Preparation method of aromatic ketone compound substituted by beta, delta-position different functional groups - Google Patents

Preparation method of aromatic ketone compound substituted by beta, delta-position different functional groups Download PDF

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CN110256249B
CN110256249B CN201910622600.4A CN201910622600A CN110256249B CN 110256249 B CN110256249 B CN 110256249B CN 201910622600 A CN201910622600 A CN 201910622600A CN 110256249 B CN110256249 B CN 110256249B
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杨罗
武传硕
刘任翔
李立
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Xiangtan University
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Abstract

The invention discloses a preparation method of aromatic ketone compounds substituted by beta, delta-position different functional groups. The method takes aromatic aldehyde, electron-deficient olefin, styrene derivative and tert-butyl hydroperoxide as reaction substrates, and generates free radical tandem reaction under the catalysis of transition metal to generate peroxide; then adding alkali into the reaction system to directly convert the peroxide into aromatic ketone compounds substituted by beta, delta-position different functional groups. The method uses tert-butyl hydroperoxide as a free radical initiator and an oxidant to convert aromatic aldehyde into acyl free radicals; then, the acyl free radical sequentially adds the electron-deficient olefin (such as acrylic ester, acrylonitrile and acrylamide compounds) and the styrene derivative, and finally, the acyl free radical is coupled with tertiary butyl hydroperoxide to obtain corresponding peroxide; the newly generated peroxide is rearranged by Kornblum-DeLaMare under the action of alkali, and the aromatic ketone compound substituted by beta, delta-position different functional groups is obtained through one-pot reaction. The reaction temperature is 25-150 ℃ and the reaction time is 0.1-72 hours. The method overcomes the defects of complex synthesis steps and poor selectivity of aromatic ketone compounds substituted by beta, delta-position different functional groups in the traditional method. Compared with the existing method, the method has the advantages that: the double-functional reaction and cross coupling of two olefins are realized by one-time reaction, 3 new chemical bonds are constructed, and two new functional groups are introduced into an aromatic ketone product; the method has the advantages of low cost and easy acquisition of raw materials, simple operation, safer, more economic and effective, insensitivity to air, moisture and light, higher yield, easy separation and purification of products and good application prospect.

Description

Preparation method of aromatic ketone compound substituted by beta, delta-position different functional groups
Technical Field
The invention relates to a preparation method of aromatic ketone compounds substituted by beta, delta-position different functional groups.
Background
The ketone compounds are compounds with carbonyl functional groups in molecules, and can perform a plurality of conversions (such as nucleophilic reactions, condensation reactions and the like) because of higher reactivity of carbonyl groups, so that the ketone compounds have very important positions in the field of organic synthesis. The ketone compounds with different functional groups substituted in the molecule have more abundant and diverse reaction sites, and can react in the molecule or between the molecules to synthesize a plurality of molecules with biological activity. Common 1, 5-dicarbonyl compounds can be used for ring closure synthesis of different heterocyclic compounds under different reaction conditions. For example, polysubstituted pyridine rings can be synthesized (Synthesis 2006,10,1664), mcMurry coupling reactions can occur on their own to form cyclopentadiene compounds (j.org.chem.2006, 71,9873), or heterocyclic compounds containing different substituents can be ring-closed synthesized (heterocylic.Commun.2003, 9,599). The traditional method for synthesizing the 1, 5-dicarbonyl compound is mainly synthesized through Michael addition reaction, but has the defects of poor selectivity and the like for substrates with other electron withdrawing substituents. In view of the above, it is very important to develop ketone compounds containing substitution of different functional groups.
Disclosure of Invention
The invention aims to provide a preparation method of aromatic ketone compounds with beta, delta-position substituted by different functional groups.
The invention is used for preparing the aromatic ketone compound substituted by beta, delta-position different functional groups, and the structural general formula is shown in formula I:
Figure SMS_1
in the general formula I, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 12 Are selected from any one of the following groups: hydrogen atom, halogen atom, amino group, nitro group, C 1 -C 6 Alkyl, benzyl, methoxy, trifluoromethyl, carboxylate, cyano, carbonyl, carboxyl, hydroxyl; r is R 11 Any one of the following groups: cyano, carbonyl, carboxylate, phosphate and amide groups.
The method for preparing the aromatic ketone compound substituted by the beta, delta-position different functional groups provided by the invention is that under the catalysis of transition metal, aromatic aldehyde shown in the structural formula II generates acyl free radicals under the initiation of tert-butyl hydroperoxide, the acyl free radicals sequentially perform free radical addition on olefin shown in the structural formulas III and IV, and then perform free radical-free radical coupling reaction with tert-butyl peroxide to obtain a compound shown in the structural formula V; then adding alkali into the reaction system, and under the action of the alkali, obtaining a compound shown in the structural formula I by one-pot reaction of peroxide shown in the structural formula V and losing one molecule of tertiary butanol;
Figure SMS_2
The reaction general formula of the method is as follows:
Figure SMS_3
the catalyst may be any one of the following compounds: ferrous chloride, ferrous acetylacetonate, nickel sulfate, and cobalt bis salicylamide ethyl. The solvent is any one of the following compounds: acetonitrile, ethyl acetate, 1, 2-dichloroethane, chlorobenzene, fluorobenzene, benzotrifluoride. The oxidant is as follows: t-butylhydroperoxide in the organic phase, t-butylhydroperoxide in the aqueous phase. The base is any one of the following compounds: 1, 4-diazabicyclo [2.2.2] octane, 1, 8-diazabicyclo undec-7-ene, triethylamine, sodium tert-butoxide, sodium hydroxide, sodium acetate, cesium carbonate, 4-dimethylaminopyridine. The catalyst is used in an amount of 0.01-150% of the molar amount of the compound shown in the structural formula III, the oxidant is used in an amount of 50-500% of the molar amount of the compound shown in the structural formula III, and the alkali is used in an amount of 10-300% of the molar amount of the compound shown in the structural formula III. In addition, the reaction temperature of the reaction is 20-150 ℃ and the reaction time is 0.1-72 hours.
The invention realizes the difunctional reaction and cross coupling of two olefins through one-time reaction, constructs 3 new chemical bonds and introduces two new functional groups into aromatic ketone products; the raw materials and the catalyst used in the invention are cheap and easy to obtain, and the operation is simple and convenient; the reaction condition is mild, the reaction is insensitive to light, air and moisture, the yield is high, and the product is easy to separate and purify, thereby having good application prospect.
Detailed Description
The present invention will be further illustrated with reference to the following specific examples, but the present invention is not limited to the following examples.
EXAMPLE 1 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound of formula Ia
The reaction formula is as follows:
Figure SMS_4
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 41.5mg of the compound represented by the structural formula Ia was isolated in 64% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.97(d,J＝8.0Hz,2H),7.87(d,J＝7.6Hz,2H),7.56(t,J＝7.2Hz,1H),7.45(t,J＝8.0Hz,2H),7.25(d,J＝8.4Hz,2H),3.70(s,3H),3.68–3.50(m,3H),3.36(dt,J＝17.6,6.0Hz,2H),2.40(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.93,197.47,174.99,144.24,136.55,134.09,133.37,129.37,128.68,128.26,128.14,52.19,39.60,39.46,35.96,21.70.
IR:3059,3029,2951,2920,1736,1685,1606,1580,1448,1436,1407,1362,1336,1224,1180,1000,912,810,755,732,690.cm -1
Elemental Anal.Cal.C 20 H 20 O 4 :C,74.06；H,6.21；O,19.73.
EXAMPLE 2 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound represented by formula Ia
The reaction formula is as follows:
Figure SMS_5
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, a magneton, ferrous acetylacetonate (1.3 mg,0.005 mmol), styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), t-butyl hydroperoxide (166.6 mg,1.0 mmol) as an organic phase having a concentration of 5.0M to 6.0M, methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) were sequentially added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, and after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was further added to the reaction system to react at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 33.0mg of the compound shown in the structural formula Ia is isolated, and the yield is 51%.
Compound structural analysis identification data are as above.
EXAMPLE 3 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound of formula Ia
The reaction formula is as follows:
Figure SMS_6
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, a magneton, nickel acetylacetonate (1.3 mg,0.005 mmol), styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), t-butyl hydroperoxide (166.6 mg,1.0 mmol) as an organic phase having a concentration of 5.0M to 6.0M, methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) were sequentially added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, and after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was further added to the reaction system to react at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 38.2mg of the compound represented by the structural formula Ia was isolated in 59% yield.
Compound structural analysis identification data are as above.
EXAMPLE 4 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound of formula Ia
The reaction formula is as follows:
Figure SMS_7
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, a magnet, nickel sulfate (1.3 mg,0.005 mmol), styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), t-butyl hydroperoxide (166.6 mg,1.0 mmol) as an organic phase having a concentration of 5.0M to 6.0M, methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) were sequentially added under an air atmosphere, the reaction tube was sealed, then placed in an oil bath at 90℃for reaction for 12 hours, heating was stopped, and after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was further added to the reaction system, the reaction was continued at 90℃for 12 hours, and the heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 33.0mg of the compound shown in the structural formula Ia is isolated, and the yield is 51%.
Compound structural analysis identification data are as above.
EXAMPLE 5 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound of formula Ia
The reaction formula is as follows:
Figure SMS_8
The specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tolualdehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, and ethyl acetate (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) under an air atmosphere, sealing the reaction tube, placing in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, ethyl acetate is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 34.3mg of the compound represented by the structural formula Ia was isolated in 53% yield.
Compound structural analysis identification data are as above.
EXAMPLE 6 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound of formula Ia
The reaction formula is as follows:
Figure SMS_9
The specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, a magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), t-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase having a concentration of 5.0M to 6.0M, and 1, 2-dichloroethane (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) were sequentially added under an air atmosphere, the reaction tube was sealed, then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution was cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was further added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, the 1, 2-dichloroethane is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and the mixed solvent of ethyl acetate and petroleum ether (1:8) is used for leaching. 27.2mg of the compound represented by the structural formula Ia was isolated in 42% yield.
Compound structural analysis identification data are as above.
EXAMPLE 7 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound represented by formula Ia
The reaction formula is as follows:
Figure SMS_10
The specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tolualdehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube into an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 4-diazabicyclo [2.2.2] octane (33.6 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 38.9mg of the compound shown in the structural formula Ia is isolated, and the yield is 60 percent
Compound structural analysis identification data are as above.
EXAMPLE 8 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid methyl ester Compound represented by formula Ia
The reaction formula is as follows:
Figure SMS_11
the specific preparation method comprises the following steps:
In a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tolualdehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube into an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding triethylamine (30.3 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 38.9mg of the compound shown in the structural formula Ia is isolated, and the yield is 60%.
Compound structural analysis identification data are as above.
EXAMPLE 9 preparation of methyl 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyrate Compound of formula Ia
The reaction formula is as follows:
Figure SMS_12
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tolualdehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) under an air atmosphere, sealing the reaction tube, placing in an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding potassium tert-butoxide (33.6 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 32.4mg of the compound represented by the structural formula Ia was isolated in 50% yield.
Compound structural analysis identification data are as above.
EXAMPLE 10 preparation of methyl 4-oxo-2- (2-oxo-2-phenylethyl) -4-phenylbutyrate of formula Ib
The reaction formula is as follows:
Figure SMS_13
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), benzaldehyde (84.8 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) in an air atmosphere, sealing the reaction tube, placing in an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 35.3mg of the compound represented by the formula Ib is isolated in 57% yield.
The product is a solid;
melting point mp:72-73.5 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.01–7.93(m,4H),7.63–7.52(m,2H),7.50–7.41(m,4H),3.71(s,3H),3.70–3.62(m,1H),3.58(dd,J＝18.0,5.6Hz,2H),3.38(dd,J＝18.0,6.4Hz,2H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.95,174.99,136.56,133.49,128.76,128.21,52.32,39.61,35.95.
IR:3060,2951,1736,1684,1596,1580,1448,1403,1362,1335,1268,1220,1000,754,688.cm -1
Elemental Anal.Cal.C 19 H 18 O 4 :C,73.53；H,5.85；O,20.62.
EXAMPLE 11 preparation of methyl 4- (4- (tert-butyl) phenyl) -4-oxo-2- (2-oxo-2-phenylethyl) butyrate of formula Ic
The reaction formula is as follows:
Figure SMS_14
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tert-butylbenzaldehyde (129.6 mg,0.8 mmol), tert-butylhydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath pot at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 44.7mg of the compound of formula Ic was isolated in 61% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ，TMS)δ8.02–7.86(m,4H),7.60–7.52(m,1H),7.51–7.40(m,4H),3.70(s,3H),3.69–3.51(m,3H),3.42–3.31(m,2H),1.33(s,9H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.00,197.56,175.06,157.26,136.57,133.99,133.44,128.73,128.20,128.18,125.70,52.28,39.61,39.51,35.97,35.24,31.17.
IR:3349,3060,3028,2962,2869,2255,1735,1685,1604,1580,1567,1493,1448,1436,1406,1363,1335,1269,1223,1108,1050,1026,991,911,828,756,734,690.cm -1
Elemental Anal.Cal.C 23 H 26 O 4 :C,75.38；H,7.15；O,17.46.
EXAMPLE 12 preparation of methyl 4- (4-methoxyphenyl) -4-oxo-2- (2-oxo-2-phenylethyl) butyrate of formula Id
The reaction formula is as follows:
Figure SMS_15
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methoxybenzaldehyde (108.8 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 41.5mg of the compound of formula Id was isolated in 61% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.96(t,J＝7.2Hz,4H),7.56(t,J＝7.6Hz,1H),7.45(t,J＝7.6Hz,2H),6.93(d,J＝8.4Hz,2H),3.86(s,3H),3.70(s,3H),3.68–3.47(m,3H),3.43–3.27(m,2H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.97,196.32,175.03,163.73,136.56,133.36,130.42,129.64,128.67,128.13,113.83,55.52,52.17,39.61,39.21,36.03.
IR:3060,3004,2951,2841,1736,1681,1600,1575,1510,1448,1436,1420,1363,1308,1261,1223,1170,1112,1029,986,832,755,734,690.cm -1
Elemental Anal.Cal.C 20 H 20 O 5 :C,70.57；H,5.92；O,23.50.
EXAMPLE 13 preparation of methyl 4- (4-fluorophenyl) -4-oxo-2- (2-oxo-2-phenethyl) butyrate of formula Ie
The reaction formula is as follows:
Figure SMS_16
the specific preparation method comprises the following steps:
In a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-fluorobenzaldehyde (99.2 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, and after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system to react continuously at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 39.4mg of the compound represented by the structural formula Ie was isolated in 60% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.13–7.87(m,4H),7.58(t,J＝7.2Hz,1H),7.47(t,J＝7.6Hz,2H),7.13(t,J＝8.8Hz,2H),3.71(s,3H),3.69–3.50(m,3H),3.44–3.29(m,2H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.80,196.32,174.80,165.91(d,J＝253.5Hz),136.48,133.45,133.00(d,J＝2.7Hz),130.81(d,J＝9.3Hz),128.71,128.12,115.78(d,J＝21.8Hz),52.23,39.52,39.43,35.91.
IR:3066,3028,3001,2952,2919,2850,1735,1685,1597,1507,1448,1436,1410,1363,1335,1224,1099,1050,991,912,885,834,755,734,690.cm -1
Elemental Anal.Cal.C 19 H 17 FO:C,69.50；H,5.22；N,5.79；O,19.49.
EXAMPLE 14 preparation of methyl 4- (4-chlorophenyl) -4-oxo-2- (2-oxo-2-phenylethyl) butyrate of formula If
The reaction formula is as follows:
Figure SMS_17
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-chlorobenzaldehyde (112 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol) with an organic phase of 5.0M-6.0M concentration, methyl acrylate (17.2 mg,0.2 mmol), acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) in an air atmosphere, sealing the reaction tube, placing in an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction liquid to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 32.3mg of the compound represented by the structural formula If was isolated in 47% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.97(d,J＝7.2Hz,2H),7.91(d,J＝8.4Hz,2H),7.58(t,J＝7.6Hz,1H),7.45(dd,J＝16.4,7.6Hz,4H),3.71(s,3H),3.69–3.49(m,3H),3.45–3.27(m,2H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.76,196.73,174.74,139.81,136.46,134.86,133.47,129.57,128.99,128.72,128.12,52.26,39.51,39.48,35.88.
IR:3061,2951,2919,1736,1686,1589,1571,1488,1448,1436,1401,1363,1335,1272,1220,1175,1092,1051,991,820,757,690.cm -1
Elemental Anal.Cal.C 19 H 17 ClO 4 :C,66.19；H,4.97；Cl,10.28；O,18.56.
EXAMPLE 15 preparation of methyl 4- (4-bromophenyl) -4-oxo-2- (2-oxo-2-phenylethyl) butyrate of formula Ig
The reaction formula is as follows:
Figure SMS_18
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-bromobenzaldehyde (147.1 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 32.6mg of the compound of formula Ig was isolated in 42% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.97(d,J＝7.6Hz,2H),7.83(d,J＝8.4Hz,2H),7.63–7.54(m,3H),7.47(t,J＝7.6Hz,2H),3.71(s,3H),3.68–3.49(m,3H),3.39(dd,J＝18.0,6.8Hz,1H),3.32(dd,J＝18.0,6.4Hz,1H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.86,197.04,174.84,136.50,135.31,133.58,132.09,129.75,128.81,128.70,128.21,52.38,39.57,39.52,35.92.
IR:3061,2950,2922,1736,1685,1585,1448,1436,1398,1362,1335,1270,1220,1177,1070,990,814,756.cm -1
Elemental Anal.Cal.C 19 H 17 BrO 4 :C,58.63；H,4.40；Br,20.53；O,16.44.
EXAMPLE 16 preparation of methyl 4-oxo-2- (2-oxo-2- (m-tolyl) ethyl) -4-phenylbutyrate of formula Ih
The reaction formula is as follows:
Figure SMS_19
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), M-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 32.4mg of the compound represented by the structural formula Ih was isolated in 50% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.97(d,J＝7.6Hz,2H),7.77(d,J＝8.0Hz,2H),7.57(t,J＝7.2Hz,1H),7.46(t,J＝7.6Hz,2H),7.41–7.31(m,2H),3.71(s,3H),3.69–3.61(m,1H),3.57(ddd,J＝16.8,6.8,2.4Hz,2H),3.37(ddd,J＝16.6,7.8,2.8Hz,2H),2.40(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.14,198.00,175.05,138.58,136.61,136.59,134.25,133.49,128.77,128.65,128.22,125.43,52.32,39.67,39.64,35.98,21.47.
IR:3351,3060,2951,2921,1736,1685,1597,1585,1448,1435,1406,1362,1335,1218,1159,1093,1041,1000,787,754,689.cm -1
Elemental Anal.Cal.C 20 H 20 O 4 :C,74.06；H,6.21；O,19.73.
EXAMPLE 17 preparation of methyl 4-oxo-2- (2-oxo-2- (o-tolyl) ethyl) -4-phenylbutyrate of formula Ii
The reaction formula is as follows:
Figure SMS_20
the specific preparation method comprises the following steps:
In a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), o-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 43.4mg of the compound represented by the structural formula Ii was isolated in 67% yield.
The product is a solid;
melting point mp:68.8-69.5 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.02–7.93(m,2H),7.69(d,J＝7.2Hz,1H),7.61–7.54(m,1H),7.47(t,J＝8.0Hz,2H),7.37(t,J＝7.6,1.2Hz,1H),7.25(t,J＝8.0Hz,2H),3.71(s,3H),3.69–3.61(m,1H),3.57(dd,J＝17.6,5.6Hz,1H),3.48(dd,J＝18.0,6.4Hz,1H),3.36(dd,J＝18.0,6.8Hz,1H),3.27(dd,J＝18.0,6.0Hz,1H),2.49(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ201.73,197.88,175.03,138.50,137.21,136.50,133.51,132.13,131.71,128.81,128.77,128.18,125.84,52.31,42.27,39.65,36.13,21.53.
IR:3351,3061,2951,2925,2361,1736,1684,1597,1580,1486,1448,1435,1404,1360,1332,1220,1048,981,754.cm -1
Elemental Anal.Cal.C 20 H 20 O 4 :C,74.06；H,6.21；O,19.73.
EXAMPLE 18 preparation of methyl 4- (naphthalen-2-yl) -4-oxo-2- (2-oxo-2-phenylethyl) butyrate of formula Ij
The reaction formula is as follows:
Figure SMS_21
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), 2-naphthaldehyde (124.8 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) in an air atmosphere, sealing the reaction tube, placing in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 28.8mg of the compound represented by the structural formula Ij was isolated in 40% yield.
The product is a solid;
melting point mp:98.6-100.4 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.50(s,1H),8.08–7.92(m,4H),7.88(t,J＝8.4Hz,2H),7.66–7.51(m,3H),7.46(t,J＝7.6Hz,2H),3.78–3.37(m,8H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.99,197.85,175.01,136.60,135.80,133.93,133.47,132.59,130.03,129.72,128.75,128.69,128.61,128.21,127.88,126.94,123.80,52.31,39.69,39.67,36.10..
IR:3059,2950,2921,2360,1736,1683,1627,1596,1579,1469,1448,1436,1404,1363,1333,1278,1218,1180,1124,1050,1000,943,910,858,821,753,690.cm -1
Elemental Anal.Cal.C 23 H 20 O 4 :C,76.65；H,5.59；O,17.76.
EXAMPLE 19 preparation of methyl 4-oxo-2- (2-oxo-2- (1H-pyrrol-3-yl) ethyl) -4-phenylbutyrate of formula Ik
The reaction formula is as follows:
Figure SMS_22
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), pyrrole-3-carbaldehyde (76.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube into an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 40.6mg of the compound represented by the structural formula Ik was isolated in a yield of 68%.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.97(s,1H),7.96(d,J＝7.6Hz,2H),7.56(t,J＝7.6Hz,1H),7.48–7.42(m,3H),6.77(q,J＝2.0Hz,1H),6.68–6.64(m,1H),3.69(s,3H),3.64–3.51(m,2H),3.40–3.30(m,2H),3.17(dd,J＝17.2,7.2Hz,1H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.34,193.50,175.39,136.60,133.44,128.73,128.22,125.51,123.53,119.73,108.78,52.26,40.38,39.71,36.21.
IR:3349,3064,2952,2853,1732,1684,1654,1596,1541,1503,1448,1435,1342,1306,1217,1168,1086,1050,1002,924,810,754,690.cm -1
Elemental Anal.Cal.C 17 H 17 NO 4 :C,68.21；H,5.72；N,4.68；O,21.38.
EXAMPLE 20 preparation of methyl 4-oxo-2- (2-oxo-2- (1H-pyrrol-3-yl) ethyl) -4-phenylbutyrate of formula Il
The reaction formula is as follows:
Figure SMS_23
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), thiophene-2-carbaldehyde (89.6 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube into an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 26.5mg of the compound represented by the structural formula Il was isolated in 42% yield.
The product is a solid;
melting point mp:92.6-93.6 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.97(d,J＝7.2Hz,2H),7.75(d,J＝4.0Hz,1H),7.65(d,J＝5.2Hz,1H),7.57(t,J＝7.2Hz,1H),7.46(t,J＝7.6Hz,2H),7.13(t,J＝4.4Hz,1H),3.71(s,3H),3.68–3.46(m,3H),3.39(dd,J＝18.0,6.0Hz,1H),3.32(dd,J＝17.2,6.4Hz,1H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.84,190.83,174.70,143.71,136.45,134.04,133.49,132.36,128.73,128.29,128.17,52.32,40.03,39.49,36.01.
IR:3089,2950,1735,1683,1596,1580,1518,1448,1435,1415,1360,1333,1270,1224,1059,1001,854,754,726,689.cm -1
Elemental Anal.Cal.C 17 H 16 SO 4 :C,64.54；H,5.10；O,20.23；S,10.14.
EXAMPLE 21 preparation of methyl 4- (4- (tert-butyl) phenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIa
The reaction formula is as follows:
Figure SMS_24
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, p-tert-butylstyrene (64.0 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butylhydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 50.2mg of the compound of formula IIa are isolated in 66% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.89(dd,J＝19.2,8.4Hz,4H),7.47(d,J＝8.4Hz,2H),7.25(d,J＝8.0Hz,2H),3.70(s,3H),3.68–3.59(m,1H),3.54(dd,J＝18.0,5.6Hz,2H),3.41–3.29(m,2H),2.40(s,3H),1.33(s,9H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.56,197.53,175.08,157.15,144.21,134.08,133.98,129.36,128.27,128.14,125.63,52.20,39.50,39.46,35.97,35.18,31.12,21.72.
IR:3033,2962,2869,1736,1681,1606,1571,1461,1435,1407,1363,1335,1269,1225,1181,1108,1048,996,911,810,733.cm -1
Elemental Anal.Cal.C 24 H 28 O 4 :C,75.76；H,7.42；O,16.82.
EXAMPLE 22 preparation of methyl 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4- (p-tolyl) butanoate of formula IIb
The reaction formula is as follows:
Figure SMS_25
The specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton (47.2 mg,0.4 mmol), p-methylstyrene (96.0 mg,0.8 mmol), t-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the sealable pressure-resistant reaction tube under air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 42.6mg of the compound represented by the structural formula IIb was isolated in 63% yield.
The product is a solid;
melting point mp:70.3-72.6 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.87(d,J＝8.0Hz,4H),7.25(d,J＝8.0Hz,4H),3.70(s,3H),3.67–3.59(m,1H),3.54(dd,J＝18.0,6.0Hz,2H),3.34(dd,J＝18.0,6.4Hz,2H),2.40(s,6H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.56,175.12,144.25,134.11,129.38,128.29,52.22,39.51,36.00,21.74.
IR:3030,2950,2920,1736,1681,1606,1573,1436,1407,1361,1334,1272,1225,1180,1109,1044,999,980,810.cm -1
Elemental Anal.Cal.C 21 H 22 O 4 :C,74.54；H,6.55；O,18.91.
EXAMPLE 23 preparation of methyl 4- (4-methoxyphenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIc
The reaction formula is as follows:
Figure SMS_26
The specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, sequentially adding magneton (53.6 mg,0.4 mmol) and p-methoxystyrene (96.0 mg,0.8 mmol) and p-methylbenzaldehyde, tert-butyl hydroperoxide (166.6 mg,1.0 mmol) and methyl acrylate (17.2 mg,0.2 mmol) as organic phase, and acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) under air atmosphere, sealing the reaction tube, placing in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 32.6mg of the compound of formula IIc was isolated in 46% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.95(d,J＝9.2Hz,2H),7.87(d,J＝8.0Hz,2H),7.25(d,J＝8.0Hz,2H),6.98–6.87(m,2H),3.86(s,3H),3.70(s,3H),3.66–3.58(m,1H),3.52(ddd,J＝14.8,13.6,5.6Hz,2H),3.33(ddd,J＝14.6,11.8,6.8Hz,2H),2.40(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.63,196.46,175.21,163.76,144.27,134.14,130.50,129.71,129.41,128.33,113.87,55.61,52.26,39.55,39.30,36.10,21.79.
IR:2951,1736,1680,1601,1575,1510,1436,1419,1362,1261,1226,1170,1112,1030,985,810.cm -1
Elemental Anal.Cal.C 21 H 22 O 5 :C,71.17；H,6.26；O,22.57.
EXAMPLE 24 preparation of methyl 4- (4-fluorophenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IId
The reaction formula is as follows:
Figure SMS_27
the specific preparation method comprises the following steps:
In a sealable pressure-resistant reaction tube, successively adding magneton (48.8 mg,0.4 mmol), p-fluorobenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the sealable pressure-resistant reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 37.6mg of the compound of formula IId is isolated in 55% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.00(dd,J＝8.4,6.4Hz,2H),7.87(d,J＝8.0Hz,2H),7.26(d,J＝8.0Hz,2H),7.12(t,J＝8.8Hz,2H),3.71(s,3H),3.67–3.59(m,1H),3.59–3.49(m,2H),3.42–3.28(m,2H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.40,196.38,174.92,165.89(d,J＝253.4Hz),144.32,133.99,132.98(d,J＝3.0Hz),130.81(d,J＝9.3Hz),129.38,128.24,115.76(d,J＝21.8Hz).52.23,39.45,39.40,35.91,21.70.
IR:3031,2952,2920,2256,1735,1681,1597,1574,1507,1436,1409,1362,1335,1273,1227,1157,1099,1049,998,911,835,811,733.cm -1
Elemental Anal.Cal.C 20 H 19 FO 4 :C,70.16；H,5.59；F,5.55；O,18.69.
EXAMPLE 25 preparation of methyl 4- (4-chlorophenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIe
The reaction formula is as follows:
Figure SMS_28
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton (55.2 mg,0.4 mmol), p-chlorobenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 41.5mg of the compound of formula IIe was isolated in 58% yield.
The product is a solid;
melting point mp:89.3-94.6 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.89(dd,J＝16.8,8.4Hz,4H),7.43(d,J＝8.8Hz,2H),7.26(d,J＝8.4Hz,2H),3.70(s,3H),3.69–3.59(m,1H),3.54(dt,J＝17.6,6.0Hz,2H),3.34(td,J＝18.4,6.8Hz,2H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.34,196.77,174.84,144.32,139.75,134.83,133.95,129.55,129.37,128.95,128.22,52.23,39.48,39.37,35.86,21.70.
IR:3031,2951,2920,2256,1735,1685,1606,1589,1572,1488,1436,1401,1362,1335,1224,1092,1050,996,911,812,785,731,648.cm -1
Elemental Anal.Cal.C 20 H 19 ClO 4 :C,66.95；H,5.34；Cl,9.88；O,17.84.
EXAMPLE 26 preparation of methyl 4- (4-bromophenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIf
The reaction formula is as follows:
Figure SMS_29
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton (72.8 mg,0.4 mmol), p-bromostyrene (96.0 mg,0.8 mmol), p-methylbenzaldehyde (5.0M-6.0M concentration of organic phase tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol), acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under air atmosphere, sealing the reaction tube, placing the reaction tube into an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 43.4mg of the compound represented by the formula IIf was isolated in 54% yield.
The product is a solid;
melting point mp:86.9-88.6 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.94–7.75(m,4H),7.59(d,J＝7.6Hz,2H),7.26(d,J＝8.0Hz,2H),3.70(s,3H),3.69–3.59(m,1H),3.53(ddd,J＝16.4,6.8,3.2Hz,2H),3.33(ddd,J＝21.0,18.2,6.8Hz,2H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.37,197.02,174.86,144.37,135.26,133.98,131.99,129.69,129.41,128.57,128.26,52.29,39.49,39.40,35.89,21.75.
IR:3350,3031,2950,2920,2255,1735,1685,1606,1585,1484,1436,1399,1361,1334,1273,1224,1103,1070,996,910,811,784,733.cm -1
Elemental Anal.Cal.C 20 H 19 BrO 4 :C,59.57；H,4.75；Br,19.81；O,15.87.
EXAMPLE 27 preparation of methyl 4- (3-chlorophenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIg
The reaction formula is as follows:
Figure SMS_30
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the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, M-chlorostyrene (55.2 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 35.8mg of the compound represented by the structural formula IIg was isolated in 50% yield.
The product is a solid;
melting point mp:83.2-85.5 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.93(s,1H),7.86(t,J＝8.0Hz,3H),7.53(dd,J＝8.0,0.8Hz,1H),7.40(t,J＝8.0Hz,1H),7.26(d,J＝7.2Hz,2H),3.71(s,3H),3.69–3.59(m,1H),3.54(dt,J＝18.0,7.6Hz,2H),3.34(td,J＝17.6,6.8Hz,2H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.38,196.80,174.83,144.41,138.07,135.05,134.00,133.32,130.07,129.44,128.29,126.29,52.33,39.67,39.40,35.87,21.77.
IR:3066,3030,2951,2920,2255,1735,1685,1606,1572,1435,1422,1362,1334,1267,1223,1102,1075,1049,998,910,809,785,733,682.cm -1
Elemental Anal.Cal.C 20 H 19 ClO 4 :C,66.95；H,5.34；Cl,9.88；O,17.84.
EXAMPLE 28 preparation of methyl 4- (2-chlorophenyl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIh
The reaction formula is as follows:
Figure SMS_31
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, o-chlorostyrene (55.2 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 39.4mg of the compound represented by the formula IIh was isolated in 55% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.87(d,J＝8.0Hz,2H),7.54(d,J＝8.0Hz,1H),7.45–7.21(m,5H),3.71(s,3H),3.69–3.59(m,1H),3.59–3.44(m,2H),3.44–3.22(m,2H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ200.98,197.33,174.68,144.33,138.78,134.08,132.00,131.03,130.69,129.43,129.24,128.28,127.04,52.29,43.77,39.37,36.23,21.75.
IR:2951,2921,1736,1682,1606,1590,1571,1470,1434,1407,1361,1332,1273,1224,1181,1122,1069,1037,989,810,759.cm -1
Elemental Anal.Cal.C 20 H 19 ClO 4 :C,66.95；H,5.34；Cl,9.88；O,17.84.
EXAMPLE 29 preparation of methyl 4- (naphthalen-2-yl) -4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) butyrate of formula IIi
The reaction formula is as follows:
Figure SMS_32
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, 2-vinylnaphthalene (61.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) into the reaction tube under an air atmosphere, sealing the reaction tube, placing the reaction tube in an oil bath pot at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 34.4mg of the compound of formula IIi was isolated in 46% yield.
The product is a solid;
melting point mp:108.7-110 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.50(s,1H),8.03(d,J＝8.4Hz,1H),7.96(d,J＝8.0Hz,1H),7.88(t,J＝8.0Hz,4H),7.58(dt,J＝20.4,7.2Hz,2H),7.25(d,J＝7.2Hz,2H),3.78–3.64(m,5H),3.62–3.46(m,2H),3.41(dd,J＝18.0,6.4Hz,1H),2.40(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.93,197.61,175.11,144.33,135.82,134.18,133.98,132.61,130.05,129.74,129.44,128.69,128.61,128.35,127.89,126.94,123.84,52.30,39.71,39.59,36.18,21.77.
IR:3058,2950,2922,2853,1736,1681,1627,1606,1573,1468,1435,1407,1361,1332,1278,1223,1180,1123,1049,996,857,810,748.cm -1
Elemental Anal.Cal.C 24 H 22 O 4 :C,76.99；H,5.92；O,17.09.
EXAMPLE 30 preparation of 4- (tert-butylperoxy) -2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylpentanoic acid methyl ester of formula IIj
The reaction formula is as follows:
Figure SMS_33
the specific preparation method comprises the following steps:
to a sealable pressure-resistant reaction tube was successively added, under an air atmosphere, magneton, α -methylstyrene (47.2 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), t-butylhydroperoxide (166.6 mg,1.0 mmol) as an organic phase having a concentration of 5.0M to 6.0M, methyl acrylate (17.2 mg,0.2 mmol), acetonitrile (1 ml) in which ferrous chloride (0.6 mg,0.005 mmol) was dissolved, and after sealing the reaction tube, the reaction tube was placed in an oil bath at 90℃for 12 hours and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 41.2mg of the compound of formula IIj was isolated in 50% yield, d.r. =1.5:1.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.76(dd,J＝26.8,8.4Hz,2H),7.43(t,J＝8.4Hz,2H),7.35–7.28(m,2H),7.25–7.19(m,3H),,3.56(d,J＝10.4Hz,2H),3.39(dd,J＝18.0,8.4Hz,0.6×1H),3.29–3.18(m,1H),3.18–3.12(m,0.4×1H),3.03(dd,J＝16.8,4.4Hz,0.45×1H),2.91–2.81(m,0.55×1H),2.44–2.33(m,4H),2.19(dd,J＝14.8,7.2Hz,0.6×1H),2.01(dd,J＝14.8,6.0Hz,0.4×1H),1.67(d,J＝4.4Hz,3H),1.23(d,J＝3.6Hz,9H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.95,197.79,176.22,176.17,145.02,144.10,143.94,143.87,134.39,134.24,129.29,128.24,128.20,128.02,126.98,126.92,125.93,125.70,83.89,83.26,79.36,79.25,51.89,51.86,42.73,41.73,41.39,41.03,36.95,36.67,26.85,26.83,25.95,24.49,21.74.
IR:3058,3028,2979,1950,1736,1685,1607,1573,1495,1446,1407,1362,1333,1260,1223,1181,1122,1071,1030,1003,877,809,761,733,700.cm -1
Elemental Anal.Cal.C 25 H 32 O 5 :C,72.79；H,7.82；O,19.39.
EXAMPLE 31 preparation of methyl 4- (tert-butylperoxy) -2- (2-oxo-2- (p-tolyl) ethyl) -4, 4-diphenylbutyrate of formula IIk
The reaction formula is as follows:
Figure SMS_34
the specific preparation method comprises the following steps:
to a sealable pressure-resistant reaction tube was successively added magneton, 1-stilbene (72.0 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), t-butylhydroperoxide (166.6 mg,1.0 mmol), methyl acrylate (17.2 mg,0.2 mmol) and acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) under an air atmosphere, and the reaction tube was sealed and placed in an oil bath at 90℃to react for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 36.0mg of the compound of formula IIj was isolated in 38% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.73(d,J＝8.4Hz,2H),7.41–7.06(m,12H),3.49(s,3H),3.34(dd,J＝17.2,8.0Hz,1H),3.12–2.99(m,2H),2.82(dd,J＝15.6,8.4Hz,1H),2.38(s,3H),1.03(s,9H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.07,176.39,144.46,143.81,143.67,134.30,129.24,128.25,127.85,127.79,127.66,127.19,127.09,86.25,79.64,51.83,41.05,37.42,36.46,26.60,21.74.
IR:3089,3058,3027,2979,2949,2254,1735,1684,1607,1573,1447,1405,1363,1332,1258,1195,1118,1059,1031,1002,956,911,879,809,777,755,733,699.cm -1
Elemental Anal.Cal.C 30 H 34 O 5 :C,75.92；H,7.22；O,16.86.
EXAMPLE 32 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutanoic acid butyl ester of formula IIIa
The reaction formula is as follows:
Figure SMS_35
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), butyl acrylate (25.6 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, then placed in an oil bath at 90℃for reaction for 12 hours, heating was stopped, after the reaction solution was cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and the heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 40.2mg of the compound represented by the structural formula IIIa is isolated in 55% yield.
The product is a solid;
melting point mp:81.6-83.6 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.00–7.93(m,2H),7.87(d,J＝8.0Hz,2H),7.56(t,J＝7.2Hz,1H),7.45(t,J＝7.6Hz,2H),7.25(d,J＝8.0Hz,2H),4.10(t,J＝6.8Hz,2H),3.76–3.45(m,3H),3.34(dt,J＝17.6,5.6Hz,2H),2.40(s,3H),1.60–1.50(m,2H),1.36–1.24(m,2H),0.86(t,J＝7.6Hz,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.08,197.63,174.58,144.26,136.64,134.17,133.40,129.41,128.72,128.31,128.20,64.97,39.62,39.48,36.20,30.60,21.78,19.19,13.77.
IR:3350,3060,3029,2959,2872,1731,1682,1606,1580,1449,1408,1361,1333,1180,1102,1063,1001,887,842,810,755,690.cm -1
Elemental Anal.Cal.C 23 H 26 O 4 :C,75.38；H,7.15；O,17.46.
EXAMPLE 33 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyric acid benzyl ester of formula IIIb
The reaction formula is as follows:
Figure SMS_36
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), benzyl acrylate (32.4 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 44.0mg of the compound represented by the structural formula IIIb is isolated in 55% yield.
The product is a solid;
melting point mp:88.6-89.5 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.94(d,J＝7.6Hz,2H),7.84(d,J＝8.4Hz,2H),7.54(t,J＝7.2Hz,1H),7.43(t,J＝7.6Hz,2H),7.23(d,J＝8.0Hz,2H),5.14(s,2H),3.75–3.66(m,1H),3.56(ddd,J＝15.0,12.6,6.0Hz,2H),3.45–3.30(m,2H),2.39(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ197.94,197.48,174.35,144.24,136.53,135.88,134.06,133.38,129.36,128.67,128.52,128.27,128.15,66.82,39.52,39.39,36.10,21.73.
IR:3062,3032,2920,1735,1684,1606,1580,1497,1448,1407,1361,1333,1217,1180,1102,1048,1000,846,809,753,690.cm -1
Elemental Anal.Cal.C 26 H 24 O 4 :C,77.98；H,6.04；O,15.98.
EXAMPLE 34 preparation of methyl 2-methyl-4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyrate of formula IIIc
The reaction formula is as follows:
Figure SMS_37
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tolualdehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl methacrylate (20.0 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath pot at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, and the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 26.4mg of the compound represented by the structural formula IIIc was isolated in 39% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.95–7.92(m,2H),7.84(d,J＝8.0Hz,2H),7.59–7.48(m,1H),7.46–7.40(m,2H),7.22(d,J＝8.0Hz,2H),3.72(dd,J＝17.6,15.6Hz,2H),3.65(s,3H),3.56(dd,J＝17.6,10.0Hz,2H),2.38(s,3H),1.49(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.61,198.23,177.09,144.05,137.22,134.79,133.22,129.29,128.61,128.24,128.10,52.24,44.15,43.96,42.74,23.78,21.69.
IR:3346,3059,3028,2949,1735,1685,1606,1580,1448,1434,1406,1355,1284,1204,1181,1109,1012,954,910,866,843,807,775,753,690.cm -1
Elemental Anal.Cal.C 21 H 22 O 4 :C,74.54；H,6.55；O,18.91.
EXAMPLE 34 preparation of methyl 2-methyl-4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyrate of formula IIIc
The reaction formula is as follows:
Figure SMS_38
The specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-tolualdehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), methyl methacrylate (20.0 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath pot at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, and the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 26.4mg of the compound represented by the structural formula IIIc was isolated in 39% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.95–7.92(m,2H),7.84(d,J＝8.0Hz,2H),7.59–7.48(m,1H),7.46–7.40(m,2H),7.22(d,J＝8.0Hz,2H),3.72(dd,J＝17.6,15.6Hz,2H),3.65(s,3H),3.56(dd,J＝17.6,10.0Hz,2H),2.38(s,3H),1.49(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.61,198.23,177.09,144.05,137.22,134.79,133.22,129.29,128.61,128.24,128.10,52.24,44.15,43.96,42.74,23.78,21.69.
IR:3346,3059,3028,2949,1735,1685,1606,1580,1448,1434,1406,1355,1284,1204,1181,1109,1012,954,910,866,843,807,775,753,690.cm -1
Elemental Anal.Cal.C 21 H 22 O 4 :C,74.54；H,6.55；O,18.91.
EXAMPLE 35 preparation of 4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutyronitrile of formula IIId
The reaction formula is as follows:
Figure SMS_39
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), acrylonitrile (10.6 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, and acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) under an air atmosphere, sealing the reaction tube, placing in an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction solution to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuing to react at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 29.1mg of the compound of formula IIId was isolated in 50% yield.
The product is a solid;
melting point mp:116.5-118.2 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.99–7.91(m,2H),7.85(d,J＝8.0Hz,2H),7.60(t,J＝7.2Hz,1H),7.48(t,J＝7.6Hz,2H),7.27(d,J＝8.0Hz,2H),3.89–3.79(m,1H),3.61–3.36(m,4H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ195.43,194.99,144.99,135.81,133.98,133.36,129.60,128.91,128.27,128.16,121.60,39.85,39.66,21.82,21.71.
IR:3060,2920,2243,1734,1684,1606,1580,1449,1408,1358,1265,1233,1182,1109,1000,983,904,810,753,689.cm -1
Elemental Anal.Cal.C 19 H 17 NO 2 :C,78.33；H,5.88；N,4.81；O,10.98.
EXAMPLE 36 preparation of N, N-dimethyl-4-oxo-2- (2-oxo-2- (p-tolyl) ethyl) -4-phenylbutanamide of formula IIIe
The reaction formula is as follows:
Figure SMS_40
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol) in an organic phase with a concentration of 5.0M-6.0M, N, N' -dimethylacrylamide (20.0 mg,0.2 mmol), acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) in the air, sealing the reaction tube, placing in an oil bath at 90 ℃ for reaction for 12 hours, stopping heating, cooling the reaction liquid to room temperature, adding 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) into the reaction system, continuously reacting at 90 ℃ for 12 hours, and stopping heating. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 43.8mg of the compound represented by the structural formula IIIe is isolated in 65% yield.
The product is a solid;
melting point mp:135.9-138.5 ℃;
1 H NMR(400MHz,CDCl 3 ,TMS)δ7.95(d,J＝7.6Hz,2H),7.85(d,J＝8.0Hz,2H),7.56(t,J＝7.6Hz,1H),7.45(t,J＝7.6Hz,2H),7.25(d,J＝8.4Hz,2H),4.11–3.94(m,1H),3.48(ddd,J＝21.8,17.4,7.6Hz,2H),3.31(s,3H),3.26–3.13(m,2H),2.96(s,3H),2.41(s,3H).
13 C NMR(100MHz,CDCl 3 ,TMS)δ198.48,198.00,175.12,144.27,136.64,134.18,133.40,129.41,128.71,128.30,128.18,41.54,41.34,37.86,36.07,32.24,21.78.
IR:3348,3059,3029,2924,1683,1640,1606,1579,1493,1448,1400,1358,1266,1236,1219,1180,1141,1089,1057,1000,812,759,737,690.cm -1
Elemental Anal.Cal.C 21 H 23 NO 3 :C,74.75；H,6.87；N,4.15；O,14.23.
EXAMPLE 37 preparation of diethyl (1, 5-dioxo-1-phenyl-5- (p-tolyl) pent-3-yl) phosphonate of formula IIIf
The reaction formula is as follows:
Figure SMS_41
the specific preparation method comprises the following steps:
in a sealable pressure-resistant reaction tube, successively adding magneton, styrene (41.6 mg,0.4 mmol), p-methylbenzaldehyde (96.0 mg,0.8 mmol), tert-butyl hydroperoxide (166.6 mg,1.0 mmol), diethyl vinylphosphate (32.8 mg,0.2 mmol) as an organic phase with a concentration of 5.0M to 6.0M, acetonitrile (1 ml) dissolved with ferrous chloride (0.6 mg,0.005 mmol) was added under an air atmosphere, the reaction tube was sealed, and then placed in an oil bath at 90℃to react for 12 hours, heating was stopped, after the reaction solution cooled to room temperature, 1, 8-diazabicyclo undec-7-ene (45.0 mg,0.3 mmol) was added to the reaction system, the reaction was continued at 90℃for 12 hours, and heating was stopped. After the reaction solution is cooled to room temperature, acetonitrile is removed by vacuum concentration, separation is carried out by a column chromatography method, 200-300 meshes of silica gel is used as a stationary phase, and a mixed solvent (1:8) of ethyl acetate and petroleum ether is used for leaching. 27.3mg of the compound represented by the structural formula IIIf was isolated in 34% yield.
The product is a liquid;
1 H NMR(400MHz,CDCl 3 ,TMS)δ8.05–7.94(m,2H),7.88(d,J＝8.0Hz,2H),7.57(t,J＝7.2 Hz,1H),7.46(t,J＝8.0 Hz,2H),7.26(d,J＝8.8 Hz,2H),4.16–4.04(m,4H),3.62–3.38(m,3H),3.33–3.09(m,2H),2.41(s,3H),1.26(t,J＝7.2 Hz,6H).
13 C NMR(100 MHz,CDCl 3 ,TMS)δ197.29,197.18,196.91,196.80,144.15,136.64,134.15,133.29,129.38,128.69,128.36,128.24,62.23,62.18,62.16,37.82,37.79,37.59,28.21,26.77,21.73,16.43,16.37.
IR:3464,3060,3029,2981,2907,1685,1607,1580,1448,1409,1357,1238,1182,1163,1097,1054,1025,965,881,808,754,691.cm -1
Elemental Anal.Cal.C 22 H 27 PO 3 :C,65.66；H,6.76；P,7.70；O,19.88.

Claims (1)

1. a method for preparing an aromatic ketone compound with different functional groups substituted at the beta, delta-positions, which is shown in a structural general formula of a formula I, and is characterized in that: under the catalysis of transition metal, aromatic aldehyde shown in the structural formula II generates acyl free radicals under the initiation of tert-butyl hydroperoxide, the acyl free radicals sequentially perform free radical addition on olefin shown in the structural formulas III and IV, and then perform free radical-free radical coupling reaction with tert-butyl peroxide to obtain a compound shown in the structural formula V; then adding alkali into the reaction system, and under the action of the alkali, obtaining a compound shown in the structural formula I by one-pot reaction of peroxide shown in the structural formula V and losing one molecule of tertiary butanol;
Figure FDA0004185093770000011
R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 、R 12 are selected from any one of the following groups: a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a methoxy group; r is R 11 Any one of the following groups: cyano, carboxylate, phosphate and amide groups;
the catalyst for the reaction is selected from: ferrous chloride, ferrous acetylacetonate, nickel acetylacetonate, and nickel sulfate;
the reaction solvent is selected from: acetonitrile, ethyl acetate, 1, 2-dichloroethane, chlorobenzene, fluorobenzene, benzotrifluoride;
The base is selected from: 1, 4-diazabicyclo [2.2.2] octane, 1, 8-diazabicyclo undec-7-ene, triethylamine, sodium tert-butoxide, sodium hydroxide, sodium acetate, cesium carbonate, 4-dimethylaminopyridine;
the reaction temperature of the method is 20-150 ℃ and the reaction time is 0.1-72 hours.
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